Abstract:We present the new release of the ORAC engine (Procacci et al., Comput Chem 1997, 18, 1834, a FORTRAN suite to simulate complex biosystems at the atomistic level. The previous release of the ORAC code included multiple time steps integration, smooth particle mesh Ewald method, constant pressure and constant temperature simulations. The present release has been supplemented with the most advanced techniques for enhanced sampling in atomistic systems including replica exchange with solute tempering, metadynamics and steered molecular dynamics. All these computational technologies have been implemented for parallel architectures using the standard MPI communication protocol. ORAC is an open-source program distributed free of charge under the GNU general public license (GPL) at

The Crooks equation [Eq. (10) in J. Stat. Phys. 90, 1481 (1998)], originally derived for microscopically reversible Markovian systems, relates the work done on a system during an irreversible transformation to the free energy difference between the final and the initial state of the transformation. In the present work we provide a theoretical proof of the Crooks equation in the context of constant volume, constant temperature steered molecular dynamics simulations of systems thermostated by means of the Nosé-Hoover method (and its variant using a chain of thermostats). As a numerical test we use the folding and unfolding processes of decaalanine in vacuo at finite temperature. We show that the distribution of the irreversible work for the folding process is markedly non-Gaussian thereby implying, according to Crooks equation, that also the work distribution of the unfolding process must be inherently non-Gaussian. The clearly asymmetric behavior of the forward and backward irreversible work distributions is a signature of a non-Markovian regime for the folding/unfolding of decaalanine.

Molecular dynamics calculations have been used to study structural relaxation and dynamical correlations near the glass transition in the system [Ca(N0 3 h]o.4 [KN0 3 ]o.6' As in a typical molten salt, the overall structure is determined by charge ordering. However, the radial distribution function for Ca 2 + ions is unusual in that even at high temperatures it shows a split first peak due to specific spatial correlations of the cations with the nitrate anions. Structural relaxation that accompanies cooling of the system has been characterized with the aid of the van Hove real-space correlation functions G s (r,t) for the constituent atoms (Ca, K, N, 0). The relaxation of the incoherent structure factor Fs (k,t), with a wave vector k near the peak of the static structure factor, has been investigated as a function of temperature. The results clearly reveal both the a and /3 relaxation processes; the former can be well represented by a master curve with a stretched exponential shape. An analysis of the susceptibility, which agrees qualitatively with neutron spin-echo data, suggests that the glass transition for the model occurs around 400 K. The relatively small discrepancy with the experimental transition temperature derived from neutron scattering data (366 K) is likely related to inadequacies in the model employed for the interionic interactions. The functions C1(t) and C 2 (t) , which describe the reorientational relaxation of the threefold symmetry axes of the nitrate ions, are shown to exhibit a scaling behavior analogous to that of the structure factor. In the region of the glass transition, where translational diffusion has essentially stopped, the nitrate ions continue to flip predominantly about their twofold axes.

Serial generalized ensemble simulations, such as simulated tempering, enhance phase space sampling through non-Boltzmann weighting protocols. The most critical aspect of these methods with respect to the popular replica exchange schemes is the difficulty in determining the weight factors which enter the criterion for accepting replica transitions between different ensembles. Recently, a method, called BAR-SGE, was proposed for estimating optimal weight factors by resorting to a self-consistent procedure applied during the simulation (J. Chem. Theory Comput.2010, 6, 1935-1950). Calculations on model systems have shown that BAR-SGE outperforms other approaches proposed for determining optimal weights in serial generalized ensemble simulations. However, extensive tests on real systems and on convergence features with respect to the replica exchange method are lacking. Here, we report on a thorough analysis of BAR-SGE by performing molecular dynamics simulations of a solvated alanine dipeptide, a system often used as a benchmark to test new computational methodologies, and comparing results to the replica exchange method. To this aim, we have supplemented the ORAC program, a FORTRAN suite for molecular dynamics simulations (J. Comput. Chem.2010, 31, 1106-1116), with several variants of the BAR-SGE technique. An illustration of the specific BAR-SGE algorithms implemented in the ORAC program is also provided.